N-Acetyl-Glucosamine Sensitizes Non-Small Cell Lung Cancer Cells to TRAIL-Induced Apoptosis by Activating Death Receptor 5.

BACKGROUND/AIMS: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective toxicity. However, many human non-small cell lung cancer (NSCLC) cells are partially resistant to TRAIL, thereby limiting its clinical application. Therefore, there is a need for the development of novel adjuvant therapeutic agents to be used in combination with TRAIL. METHODS: In this study, the effect of N-acetyl-glucosamine (GlcNAc), a type of monosaccharide derived from chitosan, combined with TRAIL was evaluated in vitro and in vivo. Thirty NSCLC clinical samples were used to detect the expression of death receptor (DR) 4 and 5. After GlcNAc and TRAIL co-treatment, DR expression was determined by real-time PCR and western blotting. Cycloheximide was used to detect the protein half-life to further understand the correlation between GlcNAc and the metabolic rate of DR. Non-reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to detect receptor clustering, and the localization of DR was visualized by immunofluorescence under a confocal microscope. Furthermore, a co-immunoprecipitation assay was performed to analyze the formation of death-inducing signaling complex (DISC). O-linked glycan expression levels were evaluated following DR5 overexpression and RNA interference mediated knockdown. RESULTS: We found that the clinical samples expressed higher levels of DR5 than DR4, and GlcNAc co-treatment improved the effect of TRAIL-induced apoptosis by activating DR5 accumulation and clustering, which in turn recruited the apoptosis-initiating protease caspase-8 to form DISC, and initiated apoptosis. Furthermore, GlcNAc promoted DR5 clustering by improving its O-glycosylation. CONCLUSION: These results uncovered the molecular mechanism by which GlcNAc sensitizes cancer cells to TRAIL-induced apoptosis, thereby highlighting a novel effective agent for TRAIL-mediated NSCLC-targeted therapy.

N-acetyl glucosamine and proteoglycan containing supplement improves the locomotor functions of subjects with knee pain.

The aim of this study was to investigate the effect of N-acetyl glucosamine and proteoglycan-containing supplement (NGPS) on knee pain and locomotor functions in middle-aged and elderly persons with knee pain. An open trial was conducted on 19 subjects suffering from knee pain. The subjects, aged (55.6 ± 6.9) years, were given the NGPS tablets, which they must take 3 times per day, that contain 526.5 mg of N-acetyl glucosamine (GlcNAc) and 33.6 mg of proteoglycan for 12 weeks. Subjective pain was evaluated using the Visual Analog Scale (VAS), while the function of the knee with regard to daily operation was evaluated using the Japanese Knee Osteoarthritis Score (JKOM). Walking, stair-climbing and swelling were evaluated using the Japanese Orthopedic Association Score (JOA). These items were evaluated at a baseline, and after 4, 8, and 12 weeks of NGPS treatment. The VAS scores at 8 (p = 0.004) and 12 (p < 0.001) weeks were significantly lower than that at the baseline. The JKOM total score was significantly lower at 8 and 12 weeks (p = 0.001) than that at the baseline. The JOA score in the more painful side of the leg was significantly higher at 12 weeks (p = 0.002) than that at the baseline. The present study reveals that intake of NGPS is effective for relieving knee pain and improving knee function when walking or climbing stairs, swelling and bending or stretching.

Non-pharmacological measures in preterm newborns submitted to arterial puncture / Medidas no farmacológicas en recién nacidos prematuros sometidos a la punción arterial / Medidas não farmacológicas em recém-nascidos pré-termo submetidos à punção arterial

ABSTRACT Objective: to assess pain in preterm newborns and to compare the neonatal and therapeutic variables with the total scores of the Neonatal Facial Coding System of preterm newborns submitted to arterial puncture exposed to music and 25% oral glucose. Method: a comparative study with 48 recordings of preterm newborns - Group 1, music (26); Group 2, glucose 25% (22) - individually analyzed by three trained nurses, after Kappa of at least 80%. Results: the variables and the pain scores of the groups did not present statistical significance (p < 0.05) according to the Neonatal Facial Coding System. 80.8% of the preterm infants in Group 1 had a higher quantitative score ≥ 3 in the neonatal variables (gender, type of delivery), and therapeutic variables (type of oxygen therapy, place of hospitalization, type of puncture). Conclusion: There was no difference when comparing the music and glucose 25% groups and the variables studied.

RESUMEN Objetivo: evaluar el dolor en recién nacidos prematuros y comparar las variables neonatales y terapéuticas con las puntuaciones totales del Neonatal Facial Coding System de los recién nacidos prematuros sometidos a una punción arterial expuestos a la música y glucosa al 25% por vía oral. Método: estudio comparativo con 48 fi lmaciones de los recién nacidos prematuros divididos en el Grupo 1 - música (26) y el Grupo 2 - glucosa al 25% (22). Las fi lmaciones fueron analizadas individualmente por tres enfermeras capacitadas después de coefi ciente Kappa de al menos 80%. Resultados: las variables y puntuaciones de dolor de los grupos no fueron estadísticamente signifi cativas (p<0,05) de acuerdo con el Neonatal Facial Coding System. En el Grupo 1, 80,8% de los recién nacidos prematuros mostraron mayores cantidades de puntuaciones ≥ 3 en las variables neonatales (sexo, tipo de parto) y las variables terapéuticas (tipo de la terapia de oxígeno, lugar de internación, tipo de punción). Conclusión: No hubo diferencias cuando se comparan los grupos de música y de glucosa al 25% y las variables estudiadas.

RESUMO Objetivo: avaliar a dor em recém-nascidos pré-termo e comparar as variáveis neonatais e terapêuticas com os escores totais da Neonatal Facial Coding System de recém-nascidos pré-termo submetidos à punção arterial exposto à música e glicose 25% oral. Método: estudo comparativo com 48 fi lmagens de recém-nascidos pré-termo - Grupo 1, música (26); Grupo 2, glicose 25% (22) - analisadas individualmente por três enfermeiras treinadas, após Kappa de no mínimo 80%. Resultados: as variáveis e os escores de dor dos grupos não apresentaram signifi cância estatística (p < 0,05) de acordo com o Neonatal Facial Coding System. 80,8% dos prematuros do Grupo 1 apresentaram um maior quantitativo de escores ≥ 3 nas variáveis neonatais (sexo, tipo de parto) e, variáveis terapêuticas (tipo de oxigenoterapia, local de internação, tipo de punção). Conclusão: Não houve diferença ao se comparar os grupos da música e da glicose 25% e as variáveis estudadas.

Observational study: daily treatment with a new compound "Tradamixina" plus serenoa repens for two months improved the lower urinary tract symptoms.

BACKGROUND: Lower urinary tract symptoms (LUTS) are associated with great emotional costs to individuals and substantial economic costs to society. This study seeks to evaluate the effect of a new natural compound "Tradamixina plus Serenoa Repens" in order to improve lower urinary tract symptoms. METHODS: 100 patients (≥ 45 years) who had had LUTS/BPH for >6 mo at screening and with IPSS -The international Prostate symptom scores- ≥ 13 and maximum urinary flow rate (Qmax) ≥ 4 to ≤ 15 ml/s. were recruited. The compound "Tradamixina plus Serenoa Repens" (80 mg of Alga Ecklonia Bicyclis, 100 mg of Tribulus Terrestris and 100 mg of D-Glucosamine and N-Acetyl-D-Glucosamine plus 320 mg of Serenoa Repens) was administered daily for 2 months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical urological history, clinical examination, laboratory investigations (total PSA), and instrumental examination like urolfowmetry. Efficacy measures included IPSS-International Prostate Sympto, BPH Impact Index (BII), Quality-of-Life (QoL) Index. Measures were assessed at baseline and end point (12 wk or end of therapy) and also at screening, 1 and 4 wk for IPSS, and 4 wk for BII. Statistical significance was interpreted only if the results of the preceding analysis were significant at the 0.05 level. RESULTS: After 2 months of treatment the change from baseline to week 12 relative to "Tradamixina plus Seronea Repens" in total IPSS and Qol was statistically significant. Differences from baseline in BII were statistically significant for "Tradamixina plus Seronea Repens" above all differences in BII were also significant at 4 wk (LSmean ± SE: -0.8 ± 0.2). In the distribution of subjects over the PGI-I and CGI-I response categories were significant for"Tradamixina plus Seronea Repens" (PGI-I: p = 0.001; CGI-I). We also observed a decrease of total PSA. CONCLUSION: The daily treatment with a new compound "Tradamixina plus Serenoa Repens" for 2 months improved the male sexual function , it improved the bother symptoms which affect the patient's quality of life , improved uroflowmetric parameters, and we also observed a decrease of serum PSA level.

Sexual asthenia: Tradamixina versus Tadalafil 5 mg daily.

BACKGROUND: Reduced libido is widely considered the most prominent symptomatic reflection of low testosterone (T) levels in men. Testosterone deficiency (TD) afflicts approximately 30% of men aged 40-79 years. This study seeks to evaluate the effect of a new natural compound "tradamixina "in order to improve male sexual function in elderly men, particularly libido and possible erectile dysfunction, versus administration of tadalafil 5 mg daily. METHODS: Seventy patients (67.3 ± 3.7 years) with stable marital relations and affected by reduced libido, with or without erectile dysfunction were recruited. They were randomly separated in 2 groups A-B of 35. Group A was administered twice a day a new compound "Tradamixina" (150 mg of Alga Ecklonia Bicyclis, 396 mg of Tribulus Terrestris and 144 mg of D-Glucosamine and N-Acetyl-D-Glucosamine) for two months, while Group B was administered tadalafil 5 mg daily, for two months. At visit and after 60 days of treatment patients were evaluated by means of detailed medical and sexual history, clinical examination, laboratory investigations (Total and Free T), instrumental examination (NPTR- nocturnal penile tumescence and rigidity test- with Rigiscan). Patients completed a self-administered IIEF questionnaire (The international index of erectile function) and SQoLM questionnaire (Sexual quality of life Questionnarie-Male). The results pre and post treatment were compared by Student t test (p<0.005). RESULTS: After 2 months of treatment in group A serum TT levels (230 ± 18 ng/dl vs 671 ± 14 ng/dl ) and FT levels(56 ± 2.4 pg/ml vs 120 ± 3.9 pg/ml) increased, while in group B serum TT levels (245 ± 12 ng/dl vs 247 ± 15 ng/dl ) and FT levels(53 ± 0.3 pg/ml vs 55 ± 0.5 pg/ml) increased not statistically significant. The patient's numbers with negative NPTR improved after treatment in group A and B (15 vs 18 and 13 vs 25 respectively). The IIEF total score in group A increased after treatment with tradamixina (15 ± 1.5 vs 29.77 ± 1.2); the IIEF total score in group B increased slightly (12 ± 1.3 vs 23.40 ± 1.2). The SQoLM total score improved in both groups (A:16 ± 2,3 vs 33 ± 4,1 and B: 16 ± 3,4 vs 31 ± 2,1). CONCLUSION: The treatment twice a day with "Tradamixina" for 2 months improved libido in elderly men without side effects of Tadalafil.

Suppressive effects of N-acetyl-D-glucosamine on rheumatoid arthritis mouse models.

We examined effects of N-acetyl-D: -glucosamine (GlcNAc) on rheumatoid arthritis (RA) mouse models and effects of GlcNAc and glucosamine hydrochloride (GlcN) on several serum cytokine productions in RA mouse models. SKG/jcl mice were divided into control, GlcNAc, and GlcN groups. For 56 days, the control group received normal food, the GlcNAc group received 0.5 % GlcNAc-containing food, and the GlcN group received 0.5 % GlcN-containing food. GlcNAc and GlcN equally suppressed arthritis scores and histopathological scores compared to the control group. In the GlcN group, serum tumor necrosis factor-α and interleukin (IL)-6 concentrations were significantly decreased compared to the control group. In the GlcNAc group, serum IL-10, transforming growth factor ß-1, and IL-2 concentrations were significantly increased compared to the control group. Our results indicated that GlcNAc also has suppressive effects on experimental RA in mouse models. The results of serum cytokine concentrations suggested that compared to GlcN, GlcNAc has a different suppressive mechanism in experimental RA models.

Biological activities of glucosamine and its related substances.

Glucosamine (GlcN) has been widely used to treat osteoarthritis (OA) in humans. We revealed that among GlcN-derivatives (GlcN and N-acetyl-d-glucosamine) and uronic acids (d-glucuronic acid and d-galacturonic acid), only GlcN induces the production of hyaluronic acid (HA) by synovial cells and chondrocytes, and the production level is much higher (>10-fold) in synovial cells compared with chondrocytes. Moreover, GlcN increases the expression of HA-synthesizing enzymes (HAS) in synovial cells and chondrocytes. These observations indicate that GlcN likely exhibits the chondroprotective action on OA by modulating the expression of HAS and inducing the production of HA (a major component of glycosaminoglycans contained in the synovial fluid) especially by synovial cells. The pathological change of subchondral bone is implicated in the initiation and progression of cartilage damage in OA. Thus, we further determined the effect of GlcN on the bone metabolism (osteoblastic cell differentiation). The results indicated that GlcN increases the mineralization of mature osteoblasts and the expression of middle and late stage markers (osteopontin and osteocalcin, respectively) during osteoblastic differentiation, and reduces the expression of receptor activator of NF-κB ligand (RANKL), a differentiation and activation factor for osteoclasts. These observations likely suggest that GlcN has a potential to induce the osteoblastic cell differentiation and suppress the osteoclastic cell differentiation, thereby increasing bone matrix deposition and decreasing bone resorption to modulate bone metabolism in OA.

Antilip®: treatment of subjects with high total cholesterol tolerability and efficacy in a short-term registry study.

AIM: The aim of the paper was to describe a new formula (Antilip®) consisting of very low dosages of polyglucosamine, phytosterols and Monascus purpureus. It was given to subjects affected by high cholesterol levels. METHODS: The formula was used in combination with mild physical exercise (8 MET/h/week) and mild diet (reduction of cholesterol intake through foods containing <80 mg/100 g). The product combination was tested in an 8-week registry study, comparing those subjects to 33 subjects with no Antilip® treatment but following the same mild exercise training and diet. RESULTS: Results showed that Antilip® was effective in significantly reducing the total cholesterol levels from 268+/-23.2 to 201+/-11.4, whereas in the control group the reduction was almost absent (from 273+/-27 to 267+/-28). CONCLUSION: Data shows that Antilip® is a safe and effective treatment for hypercholesterolemia.

Novel glycosaminoglycan precursors as antiamyloid agents: Part IV.

In vivo amyloids consist of two classes of constituents. The first is the disease-defining protein, beta-amyloid (Abeta), in Alzheimer's disease. The second is a set of common structural components that usually are the building blocks of basement membrane (BM), a tissue structure that serves as a scaffold onto which cells normally adhere. In vitro binding interactions between one of these BM components and amyloidogenic proteins rapidly change the conformation of the amyloidogenic protein into amyloid fibrils. The offending BM component is a heparan sulfate (HS) proteoglycan, part of which is protein and the remainder a specific linear polysaccharide, which is the portion responsible for binding and imparting the typical amyloid structure to the amyloid precursor protein/peptide. Our past work has demonstrated that agents that inhibit the binding between HS and the amyloid precursor are effective antiamyloid compounds both in vitro and in vivo. Similarly, 4-deoxy analogs of glucosamine (a precursor of HS biosynthesis) are effective antiamyloid compounds both in culture and in vivo. Our continuing work concerns (1) the testing of our 4-deoxy compounds in a mouse transgenic model of Alzheimer's disease, and (2) the continuing design and synthesis of modified sugar precursors of HS, which when incorporated into the polysaccharide will alter its structure so that it affects its amyloid-inducing properties. Since our previous report, 22 additional compounds have been designed and synthesized based on the known steps involved in HS biosynthesis. Of these, 12 soluble compounds have been assessed for their effect on HS biosynthesis in hepatocyte tissue cultures. In addition, one anomer of a 4-deoxy-d-glucosamine analog, which possesses AA-amyloid inhibitory properties in vivo is in the process of being assessed for its anti-Abeta activity using a murine transgenic model of brain Abeta amyloidogenesis. The majority of the novel sugars prepared to date are analogs of N-acetylglucosamine. They have been modified at the 2-N, C-3, C-4, C-3 and C-4, or C-6 positions. One compound modified at the 2-N position (QS231), which inhibits HS synthesis in hepatocyte cultures, has shown marked enhancing properties vis-à-vis AA amyloid deposition in vivo. Very instructive results with regard to HS structure and its relation to AA amyloid deposition should be forthcoming from analyses of the AA-associated HS generated with this compound.

Application of the poly-N-acetyl glucosamine-derived rapid deployment hemostat trauma dressing in severe/lethal Swine hemorrhage trauma models.

BACKGROUND: The Rapid Deployment Hemostat (RDH) Bandage was developed for the rapid control of bleeding caused by trauma. METHODS: An extremity wound involving skin, muscle, bone, and femoral arterial injury and a 1-cm vertical incision in the abdominal aorta in swine were studied to compare the RDH Bandage, a fibrin sealant dressing and gauze to restore hemostasis. The total blood loss was determined and the survival of animals was measured. RESULTS: In the extremity injury model, the RDH Bandage reduced blood loss by 63% compared with the gauze control. In the aorta arterial incision model, the RDH Bandage required a significantly lower compression time to control bleeding compared with gauze and TachoComb. The RDH Bandage was able to stop bleeding from this injury in 100% of the tests. CONCLUSION: The RDH Bandage was superior to a commercially available fibrin bandage in controlling hemorrhage, decreasing blood loss, and increasing survival.

Comparison of poly-N-acetyl glucosamine with commercially available topical hemostats for achieving hemostasis in coagulopathic models of splenic hemorrhage.

BACKGROUND: The hemostatic quality of the poly-N-acetyl glucosamine (p-GlcNAc) patch was compared with a fibrin sealant, fibrin bandage, and cellulose patch. METHODS: A 2 x 2-cm capsular strip to a depth of 3 mm of the swine spleen was used as a source of bleeding. Splenic lacerations were created in hemophilia B dogs and treated with p-GlcNAc and Surgicel. Wounds were created in rabbits and treated with p-GlcNAc at 37degreesC and after keeping body core temperature at 29degreesC. RESULTS: Poly-N-acetyl glucosamine was able to achieve hemostasis with greater efficacy than either of the fibrin-based bandages. In the hemophilia B dog study, p-GlcNAc significantly outperformed Surgicel, with p-GlcNAc achieving hemostasis in 75% of the treated wounds compared with 17% for the cellulose patch. The hypothermia study demonstrated that p-GlcNAc is equally effective at 29degreesC and at 37degreesC. CONCLUSION: Poly-N-acetyl glucosamine was effective at controlling bleeding in animals with experimentally induced or genetic coagulopathic disorders.

Randomized double-blind studies of polysaccharide gel compared with glue and other agents for hemostasis of large veins and bleeding canine esophageal or gastric varices.

BACKGROUND: The safety and efficacy of poly-N-acetyl glucosamine (p-GlcNAc) gels were compared with standard agents in three different dog studies to assess abdominal venous collaterals, bleeding esophageal varices, and bleeding gastric varices. METHODS: Adult dogs with prehepatic portal hypertension and large abdominal venous collaterals, esophageal varices, or gastric varices were studied. RESULTS: Significantly higher sclerosis rates were seen with F2 or F4 p-GlcNAc gels and standard sclerosants. F2 and F4 gels had high rates of permanent hemostasis, low rates of secondary ulceration, and significant reductions in esophageal and gastric variceal size. These results were either equivalent to or significantly better than the most commonly used gastric varix hemostatic agent (glue) or other sclerosing agents. CONCLUSION: F2 and F4 poly-N-acetyl glucosamine gels are promising therapeutic agents for venous and variceal hemostasis.

Hemostasis in the absence of clotting factors.

BACKGROUND: This study tests whether the hemostatic action of poly-N-acetyl glucosamine (p-GlcNAc) fiber material involves vasoconstrictor release leading to closure of an aortic laceration. METHODS: A 22-gauge cannula was inserted into an infrarenal aortic segment of a rat. Surrounding ligatures were tied, and the aorta was flushed with 60 mL of saline from a reservoir held at 80 cm. A 23-gauge aortic puncture was made. The time taken to empty the reservoir was recorded. RESULTS: Control patches led to an emptying time of 295 seconds, whereas p-GlcNAc patches increased this time to greater than 600 seconds. Ten minutes after patch removal, the emptying time decreased to 330 seconds. The rats were treated intravenously with endothelin receptor antagonists BQ-485 or JKC-301. The emptying time shortened to control values, despite the use of the p-GlcNAc fiber-based patch. CONCLUSION: The mechanism of hemostasis by poly-N-acetyl glucosamine involves endothelin release independent of formed elements of blood.

Novel glycosaminoglycan precursors as anti-amyloid agents, part III.

In vivo amyloids consist of two classes of constituents. The first is the disease-defining protein, e.g., amyloid beta (Abeta) in Alzheimer's disease (AD). The second is a set of common structural components that usually are the building blocks of basement membrane (BM), a tissue structure that serves as a scaffold onto which cells normally adhere. In vitro binding interactions between one of these BM components and amyloidogenic proteins rapidly change the conformation of the amyloidogenic protein into amyloid fibrils. The offending BM component is a heparan sulfate (HS) proteoglycan (HSPG), part of which is protein, and the remainder is a specific linear polysaccharide that is the portion responsible for binding and imparting the typical amyloid structure to the amyloid precursor protein/peptide. Our past work has demonstrated that agents that inhibit the binding between HS and the amyloid precursor are effective antiamyloid compounds both in vitro and in vivo. Similarly, 4-deoxy analogs of glucosamine (a precursor of HS biosynthesis) are effective antiamyloid compounds both in culture and in vivo. Our continuing work concerns (1) the testing of our 4-deoxy compounds in a mouse transgenic model of AD, and (2) the continuing design and synthesis of modified sugar precursors of HS, which when incorporated into the polysaccharide will alter its structure so that it loses its amyloid-inducing properties. Since our previous report, 14 additional compounds have been designed and synthesized based on the known steps involved in HS biosynthesis. Of these, eight have been assessed for their effect on HS biosynthesis in hepatocyte tissue cultures, and the two anomers of a 4-deoxy-D-glucosamine analog have been assessed for their inflammation-associated amyloid (AA amyloid) inhibitory properties in vivo. The promising in vivo results with these two compounds have prompted studies using a murine transgenic model of brain Abeta amyloidogenesis. A macrophage tissue-culture model of AA amyloidogenesis has been devised based on the work of Kluve-Beckerman et al. and modified so as to assess compounds in the absence of potential in vivo confounding variables. Preliminary results indicate that the anomers of interest also inhibit AA amyloid deposition in macrophage tissue culture. Finally, an in vitro technique, using liver Golgi (the site of HS synthesis) rather than whole cells, has been devised to directly assess the effect of analogs on HS biosynthesis. The majority of the novel sugars prepared to date are analogs of N-acetylglucosamine. They have been modified either at the 2-N, C-3, C-4, or C-3 and C-4 positions. Results with the majority of the 2-N analogs suggest that hepacyte N-demethylases remove the N-substituent removal. Several of these have the desired effect on HS biosynthesis using hepatocyte cultures and will be assessed in the culture and in vivo AA amyloid models. To date 3-deoxy and 3,4-dideoxy analogs have failed to affect HS synthesis significantly. Compounds incorporating the 6-deoxy structural feature are currently being designed and synthesized.

A pilot study of N-acetyl glucosamine, a nutritional substrate for glycosaminoglycan synthesis, in paediatric chronic inflammatory bowel disease.

BACKGROUND: The breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease activity may be effective in treating chronic inflammation. AIM: To report an alternative approach, using the nutriceutical agent N-acetyl glucosamine (GlcNAc), an amino-sugar directly incorporated into glycosaminoglycans and glycoproteins, as a substrate for tissue repair mechanisms. METHODS: GlcNAc (total daily dose 3-6 g) was administered orally as adjunct therapy to 12 children with severe treatment-resistant inflammatory bowel disease (10 Crohn's disease, 2 ulcerative colitis). Seven of these children suffered from symptomatic strictures. In addition, similar doses were administered rectally as sole therapy in nine children with distal ulcerative colitis or proctitis resistant to steroids and antibiotics. Where pre- and post-treatment biopsies were available (nine cases), histochemical assessment of epithelial and matrix glycosaminoglycans and GlcNAc residues was made. FINDINGS: Eight of the children given oral GlcNAc showed clear improvement, while four required resection. Of the children with symptomatic Crohn's stricture, only 3 of 7 have required surgery over a mean follow-up of > 2.5 years, and endoscopic or radiological improvement was detected in the others. Rectal administration induced remission in two cases, clear improvement in three and no effect in two. In all cases biopsied there was evidence of histological improvement, and a significant increase in epithelial and lamina propria glycosaminoglycans and intracellular GlcNAc. CONCLUSIONS: GlcNAc shows promise as an inexpensive and nontoxic treatment in chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. It may have the potential to be helpful in stricturing disease. However, controlled trials and an assessment of enteric-release preparations are required to confirm its efficacy and establish indications for use.